天元动力系统系列报告

报告题目: A versatile novel approach for Mendelian randomization analysis with application to assess the causal effect of fetal hemoglobin on anemia in sickle cell anemia

报告人：康国莲 美国圣裘德儿童研究医院生物医学统计中心

报告时间：2022年5月23日（星期一）上午9:00-10:00

报告地点：腾讯会议在线：571-866-332  密码：123456

报告摘要： Mendelian randomization (MR) is increasingly employed as a technique to assess the causation of a risk factor on an outcome using observational data. The two-stage least-squares (2SLS) procedure is commonly used to examine the causation using genetic variants as the instrument variables. The validity of 2SLS relies on a representative sample randomly selected from the study cohort or population for genome-wide association studies (GWAS), which is not always true in practice. For example, extreme phenotype sequencing (EPS) design is widely used to investigate genetic determinants of an outcome in GWAS as it bears many advantages such as reducing sequencing or genotyping cost, improving power in detecting involvement of rare genetic variations in disease etiology and efficiency. In this paper, we develop a novel versatile and efficient approach, namely MR analysis under Extreme or random Phenotype Sampling (MREPS), for one-sample Mendelian Randomization analysis based on samples drawn through either nonrandom Extreme or random Phenotype Sampling design. In simulations, MREPS provides unbiased estimate of causal effect, correct type I error controlfor causal effect testing, is robust under different study designs, and has great power, which demonstrates the superiority of MREPS over the widely used standard 2SLS approach. We applied MREPS to assess and highlighted the causal effect of total fetal hemoglobin on anemia risk in patients with sickle cell anemia using two independent cohort studies. A user-friendly Shiny app web interface was implemented for professionals to easily explore the MREPS.

报告人简介： 康国莲博士，一直从事统计遗传、系统生物学、临床实验、和遗传流行病研究。已发表SCI学术论文124多篇，其中包括Nature Genetics, Journal of Clinical Oncology, New England Journal of Medicine等，被独立引用2400次以上。其多个研究成果被世界著名媒体报道（美国：NewsRX.com 和ScienceDaily，委内瑞拉: International Adaptogens，英国Nature Review Genetics））并被收录于书《Transgénicos》(古巴)。主持1项由美国NHLBI资助的高水平科研项目的Data Coordinating Center; 10项由美国NCI, NIH资助 的科研项目的leader biostatistician. 设计了多于50多个临床试验 protocol. 参与评审NIH(USA)和DPFS(UK)项目,是多个国际期刊的编委。